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新型Rho激酶抑制剂WAR5对阿尔茨海默病神经保护作用的研究 被引量:1

Protective effect of novel Rho kinase inhibitor WAR5 on Alzheimer Disease nerve
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摘要 目的探讨腹腔注射新型Rho激酶抑制剂WAR5对阿尔茨海默病(AD)的神经保护作用。方法16只APP/PS1双转基因小鼠随机分成2组,即AD模型组、WAR5组,每组各8只。应用Morris水迷宫实验检测各组小鼠行为学改变,蛋白质印迹法检测各组小鼠脑组织胶质细胞源性神经营养因子(GDNF)和神经营养素(NT)-3蛋白表达,免疫荧光染色检测各组小鼠脑组织GDNF和NT-3阳性表达。结果经WAR5治疗的小鼠在认知功能上优于AD组,同时WAR5能增加中枢神经系统中GDNF和NT-3等神经营养因子的表达。结论腹腔注射WAR5对AD鼠具有良好的治疗效果,可更好地改善AD模型小鼠的运动能力和空间记忆能力,所以WAR5可能成为治疗AD的一个很好的策略。 Objective To investigate the neuroprotective effect of novel Rho kinase inhibitor WAR5 by in- traperitoneal injection on Alzheimer disease (AD). Methods Sixteen APP/PS1 double transgenic mice were randomly divided into two groups, the AD model group and WARS group (n=8 each). Morris water maze test was used to deter- mine the behavioral changes of mice in each group. The GDNF and NT-3 protein expressions were examined by Western blotting. Immunohistochemical staining was used to determine the positive expression of GDNF and NT-3 in the brain tissues of mice. Results The WARS-treated mice were superior to the AD group in cognitive function, and WAR5 could increase the expression of neurotrophic factor such as GDNF and NT-3 in the central nervous system. Conclusion Intravenous injection of WAR5 shows good therapeutic effect in AD mice, which can further improve the athletic ability and spatial memory ability of AD model mice. Therefore, WAR5 may be a good strategy for the treatment of AD.
作者 周荣 王晓晖 王丽 尉杰忠 马存根 Zhou Rong Wang Xiaohui Wang Li Wei Jiezhong Ma Cungen(Department of Pathology, School of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China)
出处 《中国药物与临床》 CAS 2017年第3期309-312,共4页 Chinese Remedies & Clinics
基金 国家自然科学基金(81272163 81471412) 山西省国际科技合作项目(2013081058) 山西省回国留学人员重点科研资助项目(2014-重点7) 山西中医学院"2011"培育计划项目(2011PY-1) 山西省大同市科技局基础研究计划项目(2014105-1)
关键词 阿尔茨海默病 老年性痴呆 腹腔注射 WAR5化合物 RHO激酶抑制剂 神经营养 Alzheimer disease Intraperitoneal injection WAR5 compounds Rho kinase inhibitors Neu- rotrophy
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